Clinical Trial: Safety and Efficacy of LCI699 for the Treatment of Patients With Cushing's Disease

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase III, Multi-center, Double-blind, Randomized Withdrawal Study of LCI699 Following a 24 Week, Single-arm, Open-label Dose Titration and Treatment Period to Evaluate the Safety and Efficacy of LCI6

Brief Summary: The study aims to confirm long-term efficacy and safety of LCI699 for the treatment of patients with Cushing's disease. It is a pivotal trial intended to support the registration of LCI699 for the treatment of patients with Cushing's disease in the EU, Japan, and other countries.

Detailed Summary:
Sponsor: Novartis Pharmaceuticals

Current Primary Outcome: Proportion of randomized patients with: mUFC </= ULN [ Time Frame: Week 34 (8 weeks) ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Proportion of enrolled patients with mUFC </= ULN [ Time Frame: Week 24 ]
  To assess the complete response rate at the end of individual dose-titration and treatment with LCI699 in the initial single-arm, open label period. These patients would have had no dose increase above the level established at Week 12 between Week 13 and Week 24.
• Time-to-last control of mUFC [ Time Frame: Betwwen week 26 and week 34, up to a maximum of 8 weeks (56 days) ]
  Time-to-last control of mUFC is defined as the time (in days) from randomization to the last mUFC collection that was </= ULN before early discontinuation or completion of randomized withrdrawal period, whichever is earlier.
• Complete Response Rate (CRR) [ Time Frame: Week 12, Week 24, Week 48 ]
  Complete response rate is defined as proportion of enrolled patients with mUFC</= ULN at Week 12, Week 24 and Week 48.
• Change in mUFC [ Time Frame: baseline, post-baseline, Week 26, Week 34 ]
  Actual and percentage change in mUFC from baseline to each post-baseline visit during the core and extension at which UFC is collected. Actual and percentage change in mUFC from the time of randomization (Week 26) to the end of the randomized withdrawal period (Week 34), or the last mUFC measurement prior to early discontinuation, whichever occurs earlier.
• Change in cardiovascular-related parameters associated with Cushing's disease [ Time Frame: Baseline, Week 12, 24, 26, 34 and 48 ]
  This is for the actual and percentage change. The cardiovascular-related parameters include fasting glucose, HbA1c, fasting lipid profile, blood pressure, body weight, BMI and waist circumference.
• Change in Patient-Reported Outcomes (Health-Related Quality of Life) [ Time Frame: Baseline, Week 24, 26, 34 and 48 ]
  Change in standardized score of CushingQoL, Beck Depression Inventory-II, and EQ-5D-5L from baseline to week 24 and Week 48. Change in standardized score of CushingQoL, Beck Depression Inventory-II, and EQ-5D-5L, from the randomization (Week 26) to the end of randomized withdrawal period (Week 34), or the last measurement prior to early discontinuation, whichever occurs earlier.
• Change in the physical features of Cushing's disease by photography [ Time Frame: Weeks 12, 24, 34, and 48. ]
  Mean change from baseline to Week 12, 24, 34, and 48 in each of the following clinical signs of Cushing's disease by photography: facial rubor, hirsutism, striae, supraclavicular fat pad, dorsal fat pad, proximal muscle wasting (atrophy), central (abdominal) obesity, and ecchymoses (bruises).
• Change in bone mineral density [ Time Frame: Baseline, Week 48 ]
  Actual and percent change from baseline to Week 48 in bone mineral density as measured by DEXA scan at the lumbar spine and total hip.
• Time-to-escape [ Time Frame: At first mUFC results > 1.5 x ULN ]
  Time-to-escape is defined as time (in days) from the first mUFC </= ULN to the first mUFC results > 1.5 x ULN.
• Number of patients with adverse events (AEs) [ Time Frame: Every visit for 96 weeks ]
  For safety and tolerabuility, adverse events and laboratory abnormalities will be assessed using the National Cancer Institute-Common Toxicology Criteria (NCI-CTC) grading scale (version 4.0). AEs of special interest, as reported by the investigator, or by laboratory evaluation, electrocardiogam (ECG), Holter recording, and pituitary magnetic resonance imaging (MRI).
• Plasma concentration of LCI699 [ Time Frame: Predose, 0.5 h, 1.5 h, and 3.5 h post-dose ]
  To evaluate exposures of LCI699 in patients with Cushing's disease. Plasma concentrations (predose, 0.5 h, 1.5 h, and 3.5 h post-dose) of LCI699
• Partial Response Rate (PRR) [ Time Frame: Week 12, Week 24, Week 48 ]
  Partial response rate is defined as proportion of enrolled patients with >50% reduction from baseline in mUFC, but mUFC > ULN at Week 12, Week 24 and Week 48.
• Overall Response Rate (ORR) [ Time Frame: Week 12, Week 24, Week 48 ]
  Overall response rate is defined as proportion of enrolled patients with mUFC </= ULN or at least 50% reduction from baseline at Week 12, Week 24, Week 48.
• Actual and percentage change in mUFC [ Time Frame: Start of randomization (Week 26) to end of randomization (Week 34) ]
  Actual and percentage change in mUFC from baseline to each post-baseline visit during the core and extension at which UFC is collected. Actual and percentage change in mUFC from the time of randomization (Week 26) to the end of the randomized withdrawal period (Week 34), or the last mUFC meas
  
  

  Original Secondary Outcome: Same as current
  
  Information By: Novartis
  

  Dates:
  Date Received: June 17, 2014
  Date Started: October 6, 2014
  Date Completion: March 18, 2019
  Last Updated: March 21, 2017
  Last Verified: March 2017
  

  

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